Stereoselective synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol and its propionate, the sex pheromones of pine sawflies

Article abstract of DOI:10.1016/j.tetasy.2012.09.002

The stereoselective synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol (diprionol) and its propionate, the sex pheromones of pine sawflies (Neodiprion sp. and other), in high enantiomeric purity was achieved from (1R,3S)-2,2-dichloro-3-methylcyclopropane

Full text of DOI:10.1016/j.tetasy.2012.09.002

Tetrahedron: Asymmetry 23 (2012) 1393–1399
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Tetrahedron: Asymmetry
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Stereoselective synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol and its
propionate, the sex pheromones of pine sawflies
⇑
⇑
Vitaly Kovalenko , Evgenii Matiushenkov
Department of Organic Chemistry, Belarusian State University, Nezavisimosty Av., 4, 220030 Minsk, Belarus
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 August 2012
Accepted 11 September 2012
The stereoselective synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol (diprionol) and its propionate,
the sex pheromones of pine sawflies (Neodiprion sp. and other), in high enantiomeric purity was
achieved from (1R,3S)-2,2-dichloro-3-methylcyclopropanecarboxylic acid. The carbon skeleton of dipri-
onol was formed via copper-catalyzed cross-coupling reactions and diastereoselective methylation of
the intermediate chiral
DOL]Ti(Oi-Pr)2. The latter transformation leads to a syn-adduct with high stereoselectivity, which
depends on the presence and configuration of the -stereogenic center in the aldehyde. The diastereo-
a-methylbranched aldehyde with MeTi(Oi-Pr)3 in the presence of [(R,R)-TAD-
a
meric purity of (2S,3S,7S)-diprionol can be substantially increased via crystallization of its 3,5-
dinitrobenzoate.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
converted into diprionol 1 via stereoselective methylation with an
organometallic reagent at the final stage.
The acetate and propionate of (2S,3S,7S)-3,7-dimethylpentadec-
an-2-ol(diprionol)1 arethe principal componentsofsex pheromones
of pine sawflies (Neodiprion sp. and other).1 The attractiveness of
diprionol esters for the European pine sawfly Neodiprion sertifer1b,2
depends strongly on impurities of (2S,3R,7S)- and (2S,3R,7R)-stereo-
isomers. The efficient capture of this dangerous pest of coniferous
forests using pheromone lures requires an active ingredient in high
stereochemical purity. For this reason, approaches to the synthesis
ofdiprionol1anditsestersintheenantiomericallypureforms, aswell
as the methods for the synthesis of its stereoisomers, have been
developed intensively for several decades.3
2. Results and discussion
2.1. [(R,R)-TADDOL]Ti(OiPr)2-mediated stereoselective
methylation of 2-methyldecanal
Methylation of the key aldehyde 4 is the important final stage in
the synthesis of 1, which should predominantly lead to the product
of the addition to the carbonyl group by Cram’s rule (syn-adduct).5
However, examples on the highly diastereoselective methylation
of
a-methyl-branched aldehydes described are not numerous in
Recently, a convenient method for the resolution of the enantio-
mers of racemic trans-2,2-dichloro-3-methylcyclopropanecarboxy-
lic acid 2 and conversion into methyl-branched bifunctional chiral
building blocks (3 and its enantiomer) via a three-membered cycle
was developed.4 The easy preparation of these compounds from
available precursors provides new opportunities for the synthesis
of biologically active and practically useful compounds with a
methyl-branched carbon skeleton, in particular insect pheromones.
Taking into account the convenience of this approach, we proposed a
retrosynthetic scheme (Scheme 1) for the synthesis of 1 and its es-
ters via with the use of monoorthosuccinate (S)-3, available from
the acid (1R,3S)-2 (Fig. 1). The key methyl-branched aldehyde 4 is
the literature. The addition of organometallic reagents, such as MeLi,
MeMgBr, MeTi(OiPr)3, and Me2TiCl2 to these aldehydes proceeds
with low diastereoselectivity, and the slight prevalence of the
syn-adduct (according to Cram’s rule) or the anti-adduct (anti-Cram)
depends on the substrate and conditions.6a High diastereoselectivity
(95:5) in favor of the anti-Cram adduct was observed with the
combination of reagents Me2Zn/TiCl4.6a When using Me2Zn, similar
results in the methylation of 2-alkyl-3-(arylsulfanyl)propanals were
achieved.6b,c Similar results (up to 98:2 in favor of the anti-Cram)
were observed for the combination of methylaluminum bis(2,4,6-
tri-tert-butylphenoxide)/MeMgI.6d The chelation-controlled addi-
tion of Me2CuLi to
a-methyl-b-alkoxyaldehydes also led to the
anti-Cram adduct with high diastereoselectivity.6e The last transfor-
mation was used in the synthesis of the acetate and propionate of
diprionol 1, although it required inversion of configuration of the
carbon atom bearing the hydroxyl group via a Mitsunobu reaction
in the last stages in order to obtain the natural stereoisomer.3b
⇑
Corresponding authors. Tel.: +375 17 209 51 90; fax: +375 17 209 57 20.
E-mail addresses: kovalenkovn@rambler.ru (V. Kovalenko), matiushenkov@tut.by
(E. Matiushenkov).
0957-4166/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2012.09.002

1394
V. Kovalenko, E. Matiushenkov / Tetrahedron: Asymmetry 23 (2012) 1393–1399
Cu-catalyzed cross-coupling
C8H17
C6H13
OH
O
4
1
[(R,R)-TADDOL]Ti(OiPr)2-mediated
methylation
CO2Me
(MeO)3C
3
(S)-
ref.4
CO2H
CO2H
ref.4
Cl
rac-
Cl
Cl
(1R,3S)-
Cl
2
2
cyclopropane ring
cleavage
Scheme 1. Retrosynthetic analysis of 1.
(1S,2S,6S,10R)-1,2,6,10-Tetramethyldodecyl propanoate, the com-
ponentof the sexpheromone of thepine sawfly Microdiprion pallipes,
branched aldehydes (S)- and (R)-6 were obtained by the acid-
catalyzed hydrolysis of the acetal groups with enantiomeric purities
of at least 99% ee, which proves the high enantiomeric purity of all of
the precursors. The ee value was determined by 1H NMR spectros-
copy after reduction of the aldehyde group (LiAlH4/THF) and conver-
sion of the corresponding alcohols into esters of (S)- and (RS)-
Mosher acid.12
The alkylation of (S)-6 using MeTi(Oi-Pr)3 without the chiral
catalyst led to the preferential formation of the syn-addition prod-
uct (2S,3S)-10 according to the Cram (Felkin-Anh) model with low
diastereoselectivity (60:40) (see Table 1). This result is consistent
with published data,5 in which relatively high de values were only
obtained for substrates with aromatic substituents. The reaction of
(S)-6 with MeTi(Oi-Pr)3 in the presence of 20% of catalyst 5 led to
the syn-diastereomer (2S,3S)-10 with much greater diastereoselec-
tivity than the alkylation without the catalyst. Methylation of (R)-6
and unbranched decanal 11 exhibited lower diastereoselectivity,
but in all the cases, the stereogenic center formed in the major ste-
reoisomer had an (S)-configuration. This indicates that the chiral
catalyst performs the main stereodirecting effect during the meth-
was obtained by the reaction of the corresponding
a-methyl-
branched aldehyde with MeMgBr (Cram:anti-Cram = 2:1), but pro-
ceeded with poor diastereoselectivity.6f In order to isolate the target
syn-isomer of the alcohol, lipase PS catalyzed acetylation by vinyl
acetate was used, in which the syn-isomer remained unreacted,
while the anti-isomer underwent esterification.6f
In the recent decades, in order to obtain optically active alcohols,
reagents based on a combination of an organometallic compound
and titanium complexes with a chiral ligand (R,R)- or (S,S)-(2,2-
dimethyl-1,3-dioxolane-4,5-diyl)bis(diphenylmethanol) (TADDOL)7
such as 5 (Fig. 1) or their structural analogues have been used
widely. Examples of highly enantioselective ethylations of (R)-2-
methylhex-4-enal with Et2Zn using such catalysts to produce either
syn- or anti-isomers have been described.8a The high values of ee
[96% in favor of the (R)-isomer] were observed in the reaction of
an aliphatic unbranched aldehyde with a methylating agent based
on the titanium complex of (R,R)-TADDOL and flammable Me2Zn.8b
High ee values were obtained with MeTi(Oi-Pr)3 in the reaction of
aromatic aldehydes in the presence of TADDOL titanate,10 which is
safer to handle, easier to obtain9 and relatively more stable in stor-
age. Therefore, we chose this particular reagent for the methylation
of aldehyde 3 in the synthesis of diprionol 1. Application of the pro-
cedure and examination of stereochemical features of the methyla-
tion were carried out on substrates with simpler structures, namely
(R)- and (S)-2-methyldecanals 6. The latter aldehyde is an interme-
diate in the synthesis of diprionol 1.
ylation process, whereas the methyl substituent at the a-position
of the substrate has a negligible steric effect. Moreover, in (S)-6,
the methyl group ‘helps’ the chiral catalyst to direct the nucleo-
philic attack from the Si-side of the aldehyde group (de increases
compared to the linear aldehyde 11), while in (R)-6 it ‘hinders’
the catalyst (de decreases as compared to 11).
The data obtained can be explained by a stereochemical model
based on a combination of the Seebach model for the TADDOL
titanate catalyzed reactions of aldehydes with organometallic re-
agents10,7a and the Felkin-Anh model for the nucleophilic attack
Ph
on the carbonyl group of
a
-branched aldehydes.5 According to
Ph
O
O
O
the Seebach model, access of the nucleophile to the aldehyde car-
bonyl group coordinated with the titanium atom takes place from
the Si-side (attack from the front in Fig. 2), since in this case steric
repulsion between the phenyl groups of the ligand, the hydrocar-
bon residue of the aldehyde and the attacking nucleophile is min-
imal. At the same time, the attack of the nucleophile on the
carbonyl group of the coordinated aldehyde (S)-6 (at the Bürgi–Du-
nitz angle13,5 to the carbonyl group in the Felkin-Anh model) turns
out to be less hindered compared to (R)-6, since in the latter case
TI(OiPr)2
O
Ph
Ph
[(R,R)-TADDOL]Ti(OiPr)2
Figure 1. [(R,R)-TADDOL]Ti(OiPr)2 5.
The (S)- and (R)-succinates 3 were obtained as described above4
from 2,2-dichloro-3-methylcyclopropanecarboxylic acids (1S,3R)-
and (1R,3S)-4, respectively, and then transformed into hydroxy-
acetals (S)- and (R)-7 by treatment with LiAlH4 (Scheme 2).11 Substi-
tution of the hydroxy group with a bromine atom followed by the
Cu-catalyzed cross-coupling of bromides (S)- and (R)-8 with n-hex-
the
a-methyl group of the aldehyde causes steric hindrance
(Fig. 2). As a result, the methylation of (S)-6 proceeds with higher
diastereoselectivity than that of (R)-6.
The ratio of the methylation products was determined by 1H
NMR spectroscopy. The signals of the protons of the methyl groups
at the C-3 atom of 10 were appeared in the form of a characteristic
ylmagnesium bromide led to acetals (S)- and (R)-9.
a-Methyl-

V. Kovalenko, E. Matiushenkov / Tetrahedron: Asymmetry 23 (2012) 1393–1399
1395
CO2Me
CO2Me
MeO
MeO
(MeO)3C
(MeO)3C
X
C8H17
C8H17
(S)-6
OMe
OMe
OMe
OMe
O
O
3
(S)-
7 8
(S)- ,
9
(S)-
d
a
c
MeO
b
MeO
X
C8H17
C8H17
7 8
(R)- ,
3
(R)-
(R)-9
(R)-6
7, X=OH
8, X=Br
Scheme 2. Reagents and conditions: (a) LiAlH4, THF, reflux (83%); (b) (i) MsCl, Et3N, Et2O, 0 °C; (ii) Bu4NBr, acetone, Ref. 1 (93% for crude and 81% for purified (S)-8), 79% for
purified (R)-8, over 2 stages); (c) n-C6H13MgBr, Li2CuCl4, NMP, THF, rt (79% for (S)-9 based on (S)-7, 88% for (R)-9 based on (R)-8); (d) AcOH, HCl, H2O, rt (91%).
Table 1
Diastereoselectivity of methylation of
a-methyl-branched aldehydes 6 with MeTi(OiPr)3 mediated by [(R,R)-TADDOL]Ti(Oi-Pr)2 5 (ꢀ78 to 0 °C)
a Methylation without 5.
repulsion
Nu
C8H17
H
C8H17
CH3
H3C
H
H
Nu
O
H
O
Ti
O
O
O
Ti
O
6
(R)-
6
(S)-
Nu = nucleophilic methyltitanium species
Figure 2. Stereochemical model of [(R,R)-TADDOL]Ti(Oi-Pr)2-mediated methylation of (S)- and (R)-6 with MeTi(Oi-Pr)3.
doublet with coupling constants of 6.3–6.4 Hz. The signals for the
3.58–3.59 ppm for the esters of (S)-12 and (R)-12. The correlation
between the relative integrated intensities of the signals for the
stereoisomers of 10 and corresponding Mosher’s esters suggests
that epimerization of the enantiomerically pure aldehydes 6 does
not occur to an appreciable degree under the reaction conditions.
syn-diastereomer (2S,3S)-10 and (2R,3R)-10 were observed at a
weaker field (d = 1.14 ppm) compared to the signals for the anti-
diastereomer (2S,3R)-10 and (2R,3S)-10 (d = 1.12 ppm), which is
consistent with the literature data for compounds of similar struc-
tures.1b The de values of the alkylation products of aldehydes 6 and
11 were additionally confirmed by transformation into Mosher’s
esters12a using (S)-MTPACl followed by comparison of the integral
intensities of the signals of the methoxy groups in the 1H NMR
spectra at d = 3.52–3.53 and 3.56–3.57 ppm for the esters of
(2S,3S)-10 and (2R,3S)-10, d = 3.53–3.54 and 3.56–3.57 ppm for
the esters of (2S,3R)-10 and (2R,3R)-10, and d = 3.56–3.57 and
2.2. Synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol and its
propionate
For the synthesis of the target diprionol 1, (S)-2-methyldecanal
(S)-6 was converted into (S)-1-bromo-2-methyldecane 13 via alde-
hyde group reduction, conversion of the intermediate alcohol 14

1396
V. Kovalenko, E. Matiushenkov / Tetrahedron: Asymmetry 23 (2012) 1393–1399
into the corresponding methanesulfonate, and the substitution of
sulfonate group for a bromine atom using TBAB in acetone
(Scheme 3). The Grignard reagent obtained from bromide 13 was
used in a Li2CuCl4-catalyzed cross-coupling reaction with bro-
moacetal (S)-8 in the presence of N-methylpyrrolidinone to yield
the methyl-branched acetal 15, which had the stereogenic centers
of the required configuration.
4. Experimental
4.1. General
Solvents were dried over standard drying agents and were dis-
tilled prior to use. TLC was performed on aluminum-backed plates
coated with Silica Gel 60; chromatograms were visualized with a
Ce/Mo reagent followed by heating. Column chromatography was
performed using Merck 60 silica gel (70–230 mesh). Flash column
chromatography was carried out on Silica Gel 60 (230–240 mesh).
1H and 13C NMR spectra were recorded at 400 and 100 MHz,
respectively, in CDCl3 (CHCl3 at d = 7.26 ppm for 1H NMR and CHCl3
at d = 77.0 ppm for 13C NMR as internal standards) using a Bruker
Avance 400 spectrometer. The FT-IR spectra were recorded using
a Vertex 70 spectrometer. Optical rotations were measured at
20 °C using a CM-3 polarimeter (scale factor: 0.05°). GC–MS analy-
ses were performed using a Hewlett Packard 5890/5972 mass
spectrometer with ionization by electron impact (70 eV), with he-
lium as a carrier gas, and capillary column 50 m ꢁ 0.20 mm HP
Innovax. Melting points were determined by capillary method.
Removal of the dimethylacetal protection in compound 15 led to
the key intermediate aldehyde 4, which was subjected to methyla-
tion with MeTi(Oi-Pr)3 in the presence of [(R,R)-TADDOL]Ti(Oi-Pr)2
similar to the aldehyde (S)-6 (Section 2.1). As a result of this reaction,
the secondary alcohol 1, the product of methyl group addition
according to Cram’s model with the desired (S)-configuration at
the C-2 carbon atom, was obtained. This product contained about
5% of the (2R,3S,7S)-isomer, which was established by integration
of the signals of the C1 methyl groups of the syn- and anti-diastereo-
mers in the 1H NMR spectra at d = 1.15 ppm and 1.12 ppm, and by
derivatization with (S)-MTPACl and comparing the integral intensi-
ties of signals of the methoxy groups at d = 3.53 ppm and d 3.57 ppm.
The main (2S)-isomer of 1 was easily separated from the (2R)-
isomer by acylation with 3,5-dinitrobenzoyl chloride (DNBCl)
followed by purification of ester 16 using sequential silica gel
chromatography and crystallization from petroleum ether. Basic
methanolysis of the purified 3,5-dinitrobenzoate 16 gave alcohol
1, which contained less than 1% of the anti-diastereomer according
to the 1H NMR spectrum. The enantiomeric purity of the C2 stere-
ogenic center was established from the 1H NMR spectra of the
esters of alcohol 1 with (S)- and (RS)-Mosher acid, and reached
more than 99%. In the final stage, diprionol 1 was transformed into
propionate 17 in the usual way.3b
4.2. (S)-3-Methyl-4,4-dimethoxybutan-1-ol (S)-714
At first, LiAlH4 (7.40 g, 195 mmol) was added portionwise to a
stirred solution of (S)-methyl-4,4,4-trimethoxy-3-methylbutanoate
(S)-34 in 100 ml of THF. The resulting mixture was refluxed for 8 h
under Ar atmosphere, cooled to rt, quenched with water (7 ml),
15% aqueous NaOH (7 ml) and water (20 ml). The mixture was di-
luted with CH2Cl2 (100 ml) and filtered. The filtrate was dried over
Na2SO4 and concentrated under reduced pressure. The residue was
chromatographed on silica gel (petroleum ether/Et2O = 2/1) to give
compound (S)-7 (11.95 g, 83%); ½a D20
ꢂ
¼ ꢀ5:6 (c 3.2, Et2O); 1H NMR
3. Conclusion
(CDCl3) d 0.94 (d, J = 6.9 Hz, 3H, CH3CH), 1.41–1.49 (m, 1H, CHCH2),
1.70–1.78 (m, 1H, CHCH2), 1.89–1.99 (m, 1H, CH3CH), 2.07 (br s, 1H,
OH), 3.36 (s, 3H, CH3O), 3.39 (s, 3H, CH3O), 3.59–3.75 (m, 2H,
CH2OH), 4.08 (d, J = 6.0 Hz, 1H, CH(OCH3)2); 13C NMR (CDCl3) d
15.4 (CH3), 33.4 (CH), 35.0 (CH2), 53.8 (CH3), 54.9 (CH3), 61.0
We have obtained (2S,3S,7S)-3,7-dimethylpentadecan-2-ol 1 and
its propionate 19 with high enantiomeric purity from product (S)-3,
itself obtained from (1R,3S)-2,2-dichloro-3-methylcyclopropane-
carboxylic acid. The carbon skeleton of diprionol 1 was formed using
copper-catalyzed cross-coupling reactions and diastereoselective
(CH2), 109.0 (CH); IR (CCl4) m
max: 3487 (OH). IR and 1H NMR spectra
were similar to those for the racemic compound 7.15
methylation of the intermediate a-methylbranched aldehyde 4 with
MeTi(Oi-Pr)3 in the presence of [(R,R)-TADDOL]Ti(Oi-Pr)2. It was
shown that this conversion occurred with high diastereoselectivity
in favor of the syn-product (sin-/anti- = 95/5). The diastereomeric
purity of 1 can be substantially increased via crystallization of its
3,5-dinitrobenzoate.
4.2.1. (R)-3-Methyl-4,4-dimethoxybutan-1-ol (R)-714
This compound was obtained from (R)-34 (5.15 g, 25.0 mmol)
according to the procedure for (S)-7. Yield 3.07 g (83%);
½
a 2D0
ꢂ
¼ þ5:5 (c 3.0, Et2O). IR and NMR spectra were similar to those
for (S)-7.
a
c
d
X
MeO
MeO
C8H17
C8H17
C8H17
OMe
(S)-9
OMe
14
13
, X=OH
15
b
, X=Br
Exact Mass: 256.28
e
g
C8H17
C8H17
C8H17
O
O
Et
OH
4
17
1, (2S):(2R) = 95:5
1, (2S):(2R) > 100:1
O
f
Scheme 3. Reagents and conditions: (a) (i) AcOH, HCl, H2O, rt; (ii) LiAlH4, Et2O, ꢀ20 to 0 °C (85% over 2 stages); (b) (i) MsCl, Et3N, Et2O, 0 °C; (ii) Bu4NBr, acetone, reflux (93%
over 2 stages); (c) (i) Mg, THF; (ii) (S)-8, Li2CuCl4, NMP, THF, rt (89% based on (S)-8); (d) AcOH, HCl, H2O, rt (98% for crude 4); (e) MeTi(OiPr)3, [(R,R)-TADDOL]Ti(Oi-Pr)2,
toluene, ꢀ78 to 0 °C (86% from 15); (f) (i) DNBCl, Py, CH2Cl2, 0 °C to rt, then 2 crystallizations from petroleum ether (80%); (ii) K2CO3, MeOH, THF, 0 °C (99%); (g) EtCOCl, Py,
CH2Cl2, 0 °C to rt (93%).

V. Kovalenko, E. Matiushenkov / Tetrahedron: Asymmetry 23 (2012) 1393–1399
1397
4.3. (S)-4-Bromo-2-methyl-1,1-dimethoxybutane (S)-8
The mixture was diluted with water (10 ml) and neutralized with
solid NaHCO3. The product was extracted with Et2O (4 ꢁ 10 ml),
and the combined organic extracts were washed with brine
(10 ml), dried over Na2SO4, and concentrated under reduced pres-
sure. The residue was chromatographed on silica gel (petroleum
A solution of methanesulfonyl chloride (9.3 ml, 120 mmol) in
Et2O (30 ml) was added dropwise to a stirred and cooled to 0 °C solu-
tion of (S)-3-methyl-4,4-dimethoxybutan-1-ol (S)-7 (11.9 g,
80.3 mmol) and Et3N (22.5 ml, 162 mmol) in Et2O (80 ml). The reac-
tion mixture was stirred for 1 h at the same temperature and
quenched with saturated aqueous NaHCO3 (100 ml). The aqueous
layer was separated and extracted with ethyl acetate (3 ꢁ 50 ml).
The combined organic extracts were dried over Na2SO4 and concen-
trated under reduced pressure. The residue was dissolved in acetone
(100 ml), mixed with tetrabutylammonium bromide (38.6 g,
120 mmol) and Et3N (1.1 ml, 7.9 mmol), stirred at 55 °C for 1.5 h,
cooled to rt, and quenched with H2O (300 ml). The products were ex-
tracted with Et2O (4 ꢁ 50 ml). The combined organic extracts were
washed with H2O (30 ml), brine (30 ml), dried over Na2SO4, and con-
centrated under reduced pressure to give crude (S)-8 (15.75 g, 93%
yield). Column chromatography of crude (S)-8 (3.20 g) on silica gel
(petroleum ether/Et2O = 20/1) gave purified (S)-8 [2.79 g, 81% based
ether/Et2O = 20/1) to give (S)-6 (0.61 g, 91%); ½a D20
¼ þ13:5 (c 3.6,
ꢂ
Et2O), lit.16
½
a 2D0
ꢂ
¼ þ21:7 (c 0.58, CHCl3) for the sample with 97%
ee; 1H NMR (CDCl3) d 0.87 (t, J = 6.7 Hz, 3H, CH3CH2,), 1.07 (d,
J = 6.9 Hz, 3H, CH3CH,), 1.15–1.43 (m, 12H+1H, (CH2)6CH3 and
CHCH2), 1.63–1.72 (m, 1H, CHCH2), 2.28–2.37 (m, 1H, CH3CH),
9.60 (d, J = 2.0 Hz, 1H, CHO,]; 13C NMR (CDCl3) d 13.3 (CH3), 14.1
(CH3), 22.6 (CH2), 26.9 (CH2), 29.2 (CH2), 29.4 (CH2), 29.6 (CH2),
30.5 (CH2), 31.8 (CH2), 46.3 (CH), 205.4 (CH); IR (CCl4) mmax: 2706
(C–Hald.), 1730 (C@O).
4.5.1. (R)-2-Methyldecanal (R)-616
This compound was obtained from (R)-9 (0.85 g, 3.93 mmol)
according to the procedure for (S)-6. Yield of (R)-6 was 0.61 g
(91%); ½a 2D0
ꢂ
¼ ꢀ13:5 (c 3.6, Et2O), lit.16
½
a 2D0
ꢂ
¼ ꢀ20:2 (c 0.62, CHCl3)
on (S)-7]; ½a 2D0
ꢂ
¼ ꢀ14:5 (c 5.0, Et2O); 1H NMR (CDCl3) d 0.92 (d,
for the sample with 99% ee;. IR and NMR spectra were similar with
J = 6.8 Hz, 3H), 1.63–1.71 (m, 1H), 1.94–2.12 (m, 2H), 3.35 (s, 3H),
3.36 (s, 3H), 3.39–3.58 (m, 2H), 4.06 (d, J = 6.0 Hz, 1H); 13C NMR
(CDCl3) d 14.1 (CH3), 32.1 (CH2), 34.5 (CH), 34.9 (CH2), 54.0 (CH3),
those for (S)-10.
4.6. Methylation of (S)-6 without catalyst 5
54.5 (CH3), 108.4 (CH); IR (CCl4) mmax: 2935, 2831. Anal. Calcd for
C7H15BrO2: C, 39.83; H, 7.16. Found: C, 40.01; H, 7.19.
A solution of (S)-6 (0.34 g, 2.00 mmol) in dry toluene (2 ml) was
added dropwise to a solution of MeTi(OiPr)39 (0.72 g, 3.00 mmol) in
dry toluene (10 ml) at ꢀ78 °C under an argon atmosphere. The
mixture was warmed to 0 °C for 12 h, diluted with saturated aque-
ous NH4Cl (1 ml) and filtered. The filter cake was washed with
CH2Cl2 (2 ꢁ 5 ml). The organic phase was separated and washed
with saturated aqueous NaHCO3 (5 ml), dried over Na2SO4, and
concentrated under reduced pressure. The residue was chromato-
graphed on silica gel (petroleum ether/Et2O = 10/1) to give the
product (0.34 g, 91%) as a mixture of stereoisomers: (2S,3S)-10/
4.3.1. (R)-4-Bromo-2-methyl-1,1-dimethoxybutane (R)-8
This compound was obtained from (R)-7 (1.50 g, 10.1 mmol)
according to the procedure for (S)-8. Yield of purified (R)-8 was
1.69 g (79%); ½a 2D0
¼ þ14:0 (c 5.0, Et2O). IR and NMR spectra were
ꢂ
similar with those to (S)-8.
4.4. (S)-2-Methyl-1,1-dimethoxydecane (S)-9
A solution of n-hexylmagnesium bromide prepared from n-hex-
ylbromide (19.6 g, 119 mmol) and Mg (3.65 g, 150 mmol) in THF
(120 ml) was added dropwise to a stirred solution of crude (S)-4-bro-
mo-2-methyl-1,1-dimethoxybutane (S)-8 (12.55 g, 59.45 mmol), N-
methylpyrrolidinone-2 (45.0 g, 454 mmol), LiCl (0.20 mg, 4.7 mmol)
and anhydrous CuCl2 (0.32 g, 2.4 mmol) in dry THF (60 ml) at rt.
The reaction mixture was stirred at rt for 1 h, then quenched with sat-
urated aqueous NH4Cl (200 ml) and extracted with petroleum ether
(3 ꢁ 100 ml). The combined organic extracts were washed with satu-
rated aqueous NaHCO3 (50 ml), dried over Na2SO4, and concentrated
under reduced pressure. The residue was chromatographed on silica
gel (petroleum ether/ethyl acetate = 30/1) to give (S)-9 [10.95 g, 79%
(2R,3S)-10 = 60/40; IR (CCl4)
mmax: 3628 (OH). Anal. Calcd for
C12H26O: C, 77.35; H, 14.06. Found: C, 77.18; H, 14.02.
4.6.1. (2S,3S)-3-Methylundecan-2-ol (2S,3S)-10
1H NMR (CDCl3) d 0.88 (d, J = 6.7 Hz, 3H, CH3CH), 0.88 (t,
J = 6.9 Hz, 3H, CH3CH2), 1.07–1.45 (m, 15H, 7CH2 and CH3CH),
1.14 (d, J = 6.4 Hz, 3H, CH3CHOH), 1.60 (br s, 1H, OH), 3.67–3.73
(m, 1H, CHOH); 13C NMR (CDCl3) d 14.0 (CH3), 14.1 (CH3), 20.3
(CH3), 22.7 (CH2), 27.3 (CH2), 29.3 (CH2), 29.6 (CH2), 29.9 (CH2),
31.9 (CH2), 32.6 (CH2), 39.8 (CH), 71.4 (CH).
4.6.2. (2R,3S)-3-Methylundecan-2-ol (2R,3S)-1017
based on (S)-7]; ½a D20
ꢂ
¼ ꢀ13:5 (c 4.8, hexane); 1H NMR (CDCl3) d 0.87
1H NMR (CDCl3) d 0.86 (d, J = 6.7 Hz, 3H, CH3CH), 0.88 (t,
J = 6.9 Hz, 3H, CH3CH2), 1.06–1.49 (m, 15H, 7CH2 and CH3CH),
1.12 (d, J = 6.3 Hz, 3H, CH3CHOH), 1.58 (br s, 1H, OH), 3.63–3.69
(m, 1H, CHOH); 13C NMR (CDCl3) d 14.0 (CH3), 14.5 (CH3), 19.3
(CH3), 22.7 (CH2), 27.3 (CH2), 29.3 (CH2), 29.6 (CH2), 30.0 (CH2),
31.9 (CH2), 32.5 (CH2), 40.0 (CH), 71.8 (CH).
(t, J = 6.9 Hz, 3H, CH3CH2,), 0.88 (d, J = 6.8 Hz, 3H, CH3CH,), 1.02–1.52
(m, 14H, (CH2)7CH3), 1.66–1.76 (m, 1H, CH3CH), 3.34 (s, 6H, 2CH3O),
4.01 (d, J = 6.4 Hz, 1H, CH(OCH3)2); 13C NMR (CDCl3) d 14.1 (CH3),
14.3 (CH3), 22.7 (CH2), 26.9 (CH2), 29.3 (CH2), 29.6 (CH2), 29.9 (CH2),
31.7 (CH2), 31.9 (CH2), 35.7 (CH), 53.9 (CH3), 54.0 (CH3), 109.0 (CH);
IR (CCl4) mmax: 2928, 2856. Anal. Calcd for C13H28O2: C, 72.17; H,
13.04. Found: C, 72.25; H, 13.06.
4.7. Methylation of (S)-6, (R)-6 and 11 in the presence of
catalyst 5
4.4.1. (R)-2-Methyl-1,1-dimethoxydecane (R)-9
This compound was obtained from (R)-8 (1.00 g, 4.74 mmol)
according to the procedure for (S)-9. Yield of (R)-9 was 0.90 g
A solution of ((4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis
(diphenylmethanol) [(R,R)-TADDOL] (0.186 g, 0.40 mmol) and Ti(Oi-
Pr)4 (0.170 g, 0.60 mmol) in toluene (3 ml) was heated at 110 °C for
3 h under an argon atmosphere. The solvent was removed under re-
duced pressure, after which the residue was diluted with dry toluene
(10 ml), mixed with MeTi(OiPr)39 (0.72 g, 3.00 mmol) then cooled to
ꢀ78 °C, and stirred at this temperature for 0.5 h. The aldehyde
(2.00 mmol) was added dropwise to the resulting stirred solution at
ꢀ78 °C. The stirred mixture was warmed to 0 °C for 12 h, diluted with
saturated aqueous NH4Cl (1 ml), and filtered. The filter cake was then
(88%); ½a 2D0
¼ þ13:6 (c 6.0, hexane). IR and NMR spectra were sim-
ꢂ
ilar to those for (S)-9.
4.5. (S)-2-Methyldecanal (S)-63c,16
A mixture of (S)-2-methyl-1,1-dimethoxydecane (S)-9 (0.85 g,
3.93 mmol), AcOH (8.5 ml), water (8.5 ml) and 5% aqueous HCl
(0.08 ml) was stirred at rt for 5 h under an argon atmosphere.

1398
V. Kovalenko, E. Matiushenkov / Tetrahedron: Asymmetry 23 (2012) 1393–1399
washed with CH2Cl2 (2 ꢁ 5 ml). The organic phase was separated and
washed with saturated aqueous NaHCO3 (5 ml), dried over Na2SO4,
and concentrated under reduced pressure. The residue was chro-
matographed on silica gel (petroleum ether/Et2O = 10/1) to give the
products as the mixtures of stereoisomers with the yields and ratios
specified Table 1. The 1H and 13C NMR spectra of (2S,3S)-10 and its
enantiomer (2R,3R)-10 as well as (2R,3S)-1017 and its enantiomer
(2S,3R)-1017 obtained from these experiments were the same as in
Section 4.6.
layer was separated and extracted with Et2O (3 ꢁ 50 ml). The
combined organic extracts were dried over Na2SO4 and concen-
trated under reduced pressure. The residue was diluted with
acetone (60 ml), mixed with tetrabutylammonium bromide
(20.9 g, 65.0 mmol), and refluxed for 6 h. The reaction mixture
was cooled to rt, quenched with H2O (200 ml), and extracted with
Et2O (4 ꢁ 50 ml). The combined organic extracts were washed with
H2O (30 ml), brine (30 ml), dried over Na2SO4, and concentrated un-
der reduced pressure. The residue was chromatographed on silica
gel (petroleum ether) to give 13 (9.40 g, 93%). The spectroscopic
data were similar to those reported in the literature.12b,21
4.7.1. (S)-Undecan-2-ol (S)-12
80% ee, ½a 2D0
ꢂ
¼ þ6:0 (c 2.0, EtOH), lit.18
[a]D = +7.44 (c 1.27,
EtOH) for 99% ee. The spectroscopic data (IR, NMR) of the obtained
product were similar to those reported in the literature for rac-
13.19
4.10. (2S,6S)-2,6-Dimethyl-1,1-dimethoxytetradecane 15
A cross-coupling of purified (S)-8 (2.75 g, 13.0 mmol) with the
Grignard reagent prepared from (S)-1-bromo-2-methyldecane 13
(6.50 g, 26.3 mmol) was carried out according to the synthesis of
4.7.2. (S)-MTPA esters of 10 and 12
The stereoisomeric mixtures of (2S,3S)-10 and (2R,3S)-10,
(2S,3R)-10 and (2R,3R)-10, (S)-12 and (R)-12 were acylated with
(S)-MTPACl by Mosher’s method.12 The spectroscopic characteris-
tics of the major diastereoisomers in the mixtures are given below.
9 (Section 4.4.) to give 15 (3.33 g, 89% based on (S)-8);
½
a 2D0
ꢂ
¼ ꢀ10:1 (c 1.6, hexane); 1H NMR (CDCl3)
d 0.84 (d,
J = 6.5 Hz, 3H, CH3CH), 0.88 (t, J = 6.9 Hz, 3H, CH3CH2), 0.89 (d,
J = 6.8 Hz, 3H, CH3CHCH(OCH3)2), 1.01–1.51 (m, 21H, 10CH2 and
CHCH3), 1.68–1.77 (m, 1H, CH3CHCH(OCH3)2), 3.35 (s, 6H,
2CH3O), 4.02 (d, J = 6.5 Hz, 1H, CH(OCH3)2); 13C NMR (CDCl3) d
14.1 (CH3), 14.3 (CH3), 19.7 (CH3), 22.7 (CH2), 24.3 (CH2), 27.0
(CH2), 29.3 (CH2), 29.7 (CH2), 30.0 (CH2), 31.9 (CH2), 32.0 (CH2),
32.7 (CH), 35.7 (CH), 37.0 (CH2), 37.3 (CH2), 53.8 (CH3), 54.0
4.7.2.1. Mosher’s ester of (2S,3S)-10.
1H NMR (CDCl3) d 0.88
(t, J = 7.0 Hz, 3H, CH3CH2), 0.90 (d, J = 6.8 Hz, 3H, CH3CH), 1.06–
1.43 (m, 14H, 7CH2), 1.23 (d, J = 6.4 Hz, 3H, CH3CHO), 1.60–1.67
(m, 1H, CH3CH), 3.52–3.53 (m, 3H, CH3O), 5.06–5.12 (m, 1H,
CHO), 7.38–7.41 (m, 3H, 3CHAr), 7.51–7.53 (m, 2H, 2CHAr).
(CH3), 108.9 (CH); IR (CCl4)
mmax: 2928, 2858. Anal. Calcd for
C18H38O2: C, 75.46; H, 13.37. Found: C, 75.54; H, 13.40.
4.7.2.2. Mosher’s ester of (2S,3R)-10.
1H NMR (CDCl3) d 0.88
(t, J = 7.0 Hz, 3H, CH3CH2), 0.89 (d, J = 6.9 Hz, 3H, CH3CH), 1.06–1.43
(m, 14H, 7CH2), 1.19 (d, J = 6.4 Hz, 3H, CH3CHO), 1.71–1.78 (m, 1H,
CH3CH), 3.53–3.54 (m, 3H, CH3O), 5.04–5.10 (m, 1H, CHO), 7.38–
7.41 (m, 3H, 3CHAr), 7.51–7.54 (m, 2H, 2CHAr).
4.11. (2S,6S)-2,6-Dimethyltetradecanal 4
Aldehyde 4 was prepared from acetal 15 (3.30 g, 11.5 mmol)
according to the procedure for the hydrolysis of acetal 9 (Sec-
tion 4.5). Yield of crude aldehyde 4 was 2.72 g (98%); 1H NMR
(CDCl3) d 0.84 (d, J = 6.5 Hz, 3H), 0.88 (t, J = 6.9 Hz, 3H), 1.03–1.74
(m, 21H, 10CH2, CHCH3), 1.09 (d, J = 6.8 Hz, 3H), 2.30–2.37 (m,
1H), 9.61 (d, J = 2.0 Hz, 1H); 13C NMR (CDCl3) d 13.4 (CH3), 14.1
(CH3), 19.6 (CH3), 22.7 (CH2), 24.4 (CH2), 27.0 (CH2), 29.3 (CH2),
29.7 (CH2), 30.0 (CH2), 30.9 (CH2), 31.9 (CH2), 32.6 (CH), 36.9
4.7.2.3. Mosher’s ester of (S)-12.
1H NMR (CDCl3) d 0.88 (t,
J = 7.0 Hz, 3H, CH3CH2), 1.10–1.44 (m, 14H, 7CH2), 1.26 (d,
J = 6.0 Hz, 3H, CH3CHO), 1.51–1.60 (m, 1H, CH3CH2), 1.64–1.74
(m, 1H, CH3CH2), 3.56–3.57 (m, 3H, CH3O), 5.11–5.19 (m, 1H,
CHO), 7.38–7.42 (m, 3H, 3CHAr), 7.53–7.55 (m, 2H, 2CHAr).
(CH2), 37.0 (CH2), 46.4 (CH), 205.4 (CH); IR (CCl4)
1727. For IR and NMR spectra of rac-4 (mixture of diastereomers)
mmax: 2710,
4.8. (S)-2-Methyldecan-1-ol 1420
see Ref. 22.
(S)-2-Methyl-1,1-dimethoxydecane (S)-9 (10.90 g, 50.4 mmol)
was hydrolyzed using
a
mixture of AcOH (100 ml), water
4.12. (2S,3S,7S)-3,7-Dimethylpentadecan-2-ol(diprionol)11 from
(100 ml), and 5% aqueous HCl (1.0 ml) as described in Section 4.5.
The crude aldehyde (S)-6 was diluted with dry Et2O (50 ml) and
the solution was added dropwise to a stirred suspension of LiAlH4
(1.00 g, 26.3 mmol) in Et2O (50 ml) at ꢀ20 °C. The resulting mixture
was warmed to 0 °C and carefully quenched with 10% aqueous
H2SO4 (100 ml). The organic phase was separated, the water phase
was extracted with Et2O (3 ꢁ 50 ml), the combined organic extracts
were washed with water (20 ml), saturated aqueous NaHCO3
(20 ml), and brine (30 ml), dried over Na2SO4, and concentrated un-
der reduced pressure. The residue was chromatographed on silica
gel (petroleum ether/ethyl acetate = 10/1) to give 14 (7.40 g, 85%).
aldehyde 4
A reaction of crude aldehyde 4 (2.72 g, 11.3 mmol) with
MeTi(OiPr)3 (4.07 g, 1.5 mol equiv) in the presence of [(R,R)-TAD-
DOL]Ti(OiPr)2 (0.2 mol equiv) was carried out according to the pro-
cedure for methylation of aldehydes 6 (Section 4.7). Product 1
(2.54 g, 86% based on 15) was obtained as a mixture of (2S,3S,7S)-
and (2R,3S,7S)-diastereomers in a 95:5 ratio. The IR and 1H NMR
spectra of these diastereomers correspond to those described in
the literature.1b
½
a 2D0
ꢂ
¼ ꢀ10:0, (c 1.2, MeOH), lit.20
[
a
]
D = ꢀ9.94 (c 3.00, CH2Cl2).
4.13. (2S,3S,7S)-3,7-Dimethylpentadec-2-yl-3,5-dinitrobenzoate
16
The spectroscopic data were similar to those reported in the
literature.20
3,5-Dinitrobenzoyl chloride (3.50 g, 15.2 mmol) was added to a
4.9. (S)-1-Bromo-2-methyldecane 1312b,21
stirred solution of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol
1
[2.54 g, 9.90 mmol, (2S,3S,7S)-/(2R,3S,7S)- = 95/5] and pyridine
(5 ml, 62.0 mmol) in CH2Cl2 (20 ml) at 0 °C. The reaction mixture
was warmed to rt and stirred for 3 h, then concentrated under re-
duced pressure. The residue was diluted with 10% aqueous H2SO4
(50 ml), and extracted with Et2O (5 ꢁ 50 ml). The combined organ-
ic extracts were washed with water (30 ml), saturated aqueous
A solution of methanesulfonylchloride (5.0 ml, 65 mmol) in Et2O
(30 ml) was added dropwise to a stirred solution of (S)-2-methyld-
ecan-1-ol 14 (7.40 g, 42.9 mmol) and Et3N (12 ml, 86 mmol) in Et2O
(50 ml) at 0 °C. The reaction mixture was stirred at 0 °C for 1 h then
quenched with saturated aqueous NaHCO3 (100 ml). The aqueous

V. Kovalenko, E. Matiushenkov / Tetrahedron: Asymmetry 23 (2012) 1393–1399
1399
NaHCO3 (30 ml), brine (30 ml), dried over Na2SO4, and concen-
trated under reduced pressure. The residue was chromatographed
on silica gel (petroleum ether/ethyl acetate = 10/1) and then crys-
tallized twice from petroleum ether to give 16 (3.56 g, 80%); mp
water (20 ml), saturated aqueous NaHCO3 (20 ml), brine (20 ml),
dried over Na2SO4, and concentrated under reduced pressure. The
residue was chromatographed on silica gel (petroleum ether/ethyl
acetate = 25/1) to give 17 (2.34 g, 93%). ½a D20
¼ ꢀ5:6 (c 0.6, hexane),
ꢂ
74.5–75 °C; ½a 2D0
ꢂ
þ 19:2 (c 1.2, CHCl3). 1H NMR (CDCl3) d 0.84 (d,
lit.3b
[
a]
D = ꢀ5.7 (c 0.6, hexane), lit.23b
[
a]
D = ꢀ5.8 (c 0.35, hexane).
J = 6.5 Hz, 3H, CH3CH), 0.88 (t, J = 6.9 Hz, 3H, CH3CH2), 1.03 (d,
J = 6.9 Hz, 3H, CH3CHCHO), 1.01–1.48 (m, 21H, 10CH2 and CH3CH),
1.37 (d, J = 6.4 Hz, 3H, CH3CHO), 1.77–1.85 (m, 1H, CH3CHCHO),
5.18–5.24 (m, 1H, CHO), 9.14–9.23 (m, 3H, 3CHAr); 13C NMR
(CDCl3) d 14.1 (CH3), 14.9 (CH3), 17.0 (CH3), 19.6 (CH3), 22.6
(CH2), 24.5 (CH2), 27.0 (CH2), 29.3 (CH2), 29.6 (CH2), 30.0 (CH2),
31.9 (CH2), 32.7 (CH2), 32.9 (CH), 36.9 (CH2), 37.2 (CH2), 37.7
(CH), 77.6 (CH), 122.1 (CH), 129.3 (2CH), 134.6 (C), 148.6 (2C),
The spectroscopic data were similar to those reported in the
literature.3b,23b
Acknowledgements
This work was carried out with the support of the Forestry Min-
istry of the Republic of Belarus. We thank Mr. Aleksei Raiman for
assistance in editing of the manuscript.
162.0 (C); IR (CCl4) mmax: 3101 (CHAr), 1735 (C@O), 1542 (NO2),
1345 (NO2). Anal. Calcd for C24H38N2O6: C, 63.98; H, 8.50. Found:
References
C, 64.03; H, 8.48.
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Högberg, H.-E.; Hedenström, E.; Wassgren, A.-B.; Hjalmarsson, M.; Bergström,
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4.14. (2S,3S,7S)-3,7-Dimethylpentadecan-2-ol(diprionol) 11
from benzoate 16
At first, K2CO3 (3.50 g, 25.3 mmol) was added to a stirred solu-
tion of (2S,3S,7S)-3,7-dimethylpentadec-2-yl-3,5-dinitrobenzoate
16 (3.50 g, 7.77 mmol) in a mixture of methanol (50 ml) and THF
(50 ml) at 0 °C. The solution was stirred at 0 °C for 1 h, then diluted
with water (100 ml), and extracted with Et2O (5 ꢁ 50 ml). The
combined organic extracts were washed with brine (50 ml), dried
over Na2SO4, and concentrated under reduced pressure. The resi-
due was chromatographed on silica gel (petroleum ether/ethyl ace-
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tate = 20/1–10/1) to give alcohol
1 (1.97 g, 99%, dr 100:1)
½
a 2D0
ꢂ
¼ ꢀ11:3 (c 3.2, hexane), lit.3a
[
[
a
a
]
]
D = ꢀ9.7 (c 1.2, hexane), lit.23a
[
a
]
D = ꢀ10.4 (c 3.7, hexane), lit.23b
D = ꢀ9.9 (c 4.0, hexane); pur-
ity is >99% (by GC); MS (EI): m/z (%) = 241 (0.5) [Mꢀ15]+, 238 (0.6)
[Mꢀ18]+; IR and 1H NMR spectra were similar to those reported in
the literature.1b,12b The product was acylated with (S)- and (RS)-
MTPACl by Mosher’s method.12a The spectroscopic characteristics
of the MTPA esters are given below.
9. (a) Reetz, M. T.; Westermann, J.; Steinbach, R.; Wenderoth, B.; Peter, R.;
Ostarek, R.; Maus, S. Chem. Ber. 1985, 118, 1421–1440; (b) de Meijere, A.;
Winsel, H.; Stecker, B. Org. Synth. Coll. 2009, 11, 425–432.
ˇ
10. Ito, Y. N.; Ariza, X.; Beck, A. K.; Bobác, A.; Ganter, C.; Gawley, R. E.; Kühnle, F. N.
M.; Tuleja, J.; Wang, Y. M.; Seebach, D. Helv. Chim. Acta 1994, 77, 2071–2110.
11. This one-pot reduction of two functionalities was first performed by Vitaly
Kovalenko under supervision of Professor Oleg Kulinkovich while working on
his Ph.D. thesis. For examples of the reduction of orthoesters into acetals by
aluminum hydrides see (a) Claus, C. J.; Morgenthau, J. L. J. Am. Chem. Soc. 1951,
73, 5005; (b) Zakharkin, L. I.; Khorlina, I. M. Izv. Akad. Nauk SSSR, Ser. Khim.
1959, 8, 2255–2258; Russ. Chem. Bull. (Engl. transl.) 1959, 8, 2156–2158.; (c)
Kulinkovich, O. G.; Tischenko, I. G.; Masalov, N. V. Synthesis 1984, 886–887; (d)
Moradpour, A. J. Chem. Soc., Perkin Trans. 1 1993, 7–8.
4.14.1. Mosher’s ester of 1 with (S)-MTPACl24
1H NMR (CDCl3) d 0.83 (d, J = 6.5 Hz, 3H, CH3CH), 0.88 (t,
J = 6.9 Hz, 3H, CH3CH2), 0.90 (d, J = 6.8 Hz, 3H, CH3CHCHO), 1.00–
1.40 (m, 21H, 10CH2 and CH3CH), 1.23 (d, J = 6.4 Hz, 3H, CH3CHO),
1.61–1.70 (m, 1H, CH3CHCHO), 3.53 (s, 3H, CH3O), 5.06–5.12 (m,
1H, CHO), 7.37–7.41 (m, 3H, 3CHAr), 7.51–7.53 (m, 2H, 2CHAr).
12. (a) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34, 2543–2549; (b)
Byström, S.; Högberg, H.-E.; Norin, T. Tetrahedron 1981, 37, 2249–2254.
13. Bürgi, H. B.; Dunitz, J. D.; Lehn, J. M.; Wipff, G. Tetrahedron 1974, 30, 1563–
1572.
4.14.2. Mosher’s ester of 1 with (RS)-MTPACl
1H NMR (CDCl3) d 0.82–0.91 (m, 9H, CH3CH and CH3CH2 and
CH3CHCHO), 1.00–1.40 (m, 21H, 10CH2 and CHCH3), 1.23 (d,
J = 6.4 Hz, 1.5H, CH3CHO), 1.30 (d, J = 6.5 Hz, 1.5H, CH3CHO),
1.56–1.70 (m, 1H, CH3CHCHO), 3.53 (s, 1.5H, CH3O), 3.57 (s, 1.5H,
CH3O), 5.06–5.14 (m, 1H, CHO), 7.35–7.41 (m, 3H, 3CHAr), 7.51–
7.54 (m, 2H, 2CHAr).
14. Schmid, R.; Hansen, H.-J. Helv. Chim. Acta 1990, 73, 1258–1275.
15. Kunz, Th.; Janowitz, A.; Reißig, H.-U. Synthesis 1990, 43–47.
16. Oppolzer, W.; Darcel, Ch.; Rochet, P.; Rosset, S.; De Brabander, J. Helv. Chim.
Acta 1997, 80, 1319–1337.
17. For previously published 1H NMR and IR spectra of (2S⁄,3R⁄)-10 see: Sakai, T.;
Matsumoto, S.; Hidaka, S.; Imajo, N.; Tsuboi, S.; Utaka, M. Bull. Chem. Soc. Japan
1991, 64, 3473–3475.
18. Nakamura, K.; Matsuda, T. J. Org. Chem. 1998, 63, 8957–8964.
19. Arbain, D.; Dasman, M.; Ibrahim, S.; Sargent, M. V. Aust. J. Chem. 1990, 43,
1949–1952.
4.16. (2S,3S,7S)-3,7-Dimethylpentadec-2-yl propionate 17
20. Drewes, S. E.; Malissar, D. G. S.; Roos, G. H. P. Chem. Ber. 1993, 126, 2663–2674.
21. Francke, W.; Plass, E.; Zimmermann, N.; Tietgen, H.; Tolasch, T.; Franke, S.;
Subchev, M.; Toshova, T.; Pickett, J. A.; Wadhams, L. J.; Woodcock, C. M. J. Chem.
Ecol. 2000, 26, 1135–1150.
22. Place, P.; Roumestant, M.-L.; Gore, J. J. Org. Chem. 1978, 1001, 43.
23. (a) Kikukawam, T.; Imaida, M.; Tai, A. Bull. Chem. Soc. Japan 1984, 57, 1954–
1960; (b) Huang, P.-Q.; Lan, H.-Q.; Zheng, X.; Ruan, Y.-P. J. Org. Chem. 2004, 69,
3964–3967.
Propionyl chloride (1.40 ml, 16.1 mmol) was added dropwise to
a stirred solution of purified (2S,3S,7S)-3,7-dimethylpentadecan-2-
ol 1 (2.06 g, 8.04 mmol) and pyridine (3 ml, 37.2 mmol) in CH2Cl2
(15 ml) at 0 °C. The reaction mixture was warmed to rt and stirred
for 3 h, then concentrated under reduced pressure. The residue was
diluted with 10% aqueous H2SO4 (30 ml) and extracted with Et2O
(3 ꢁ 30 ml). The combined organic extracts were washed with
24. Mori, K.; Tamada, S. Tetrahedron 1979, 35, 1279–1284.